Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Reading DNA, Backward and Forward

Published: Monday, June 24, 2013
Last Updated: Monday, June 24, 2013
Bookmark and Share
MIT biologists reveal how cells control the direction in which the genome is read.

MIT biologists have discovered a mechanism that allows cells to read their own DNA in the correct direction and prevents them from copying most of the so-called “junk DNA” that makes up long stretches of our genome.

Only about 15 percent of the human genome consists of protein-coding genes, but in recent years scientists have found that a surprising amount of the junk, or intergenic DNA, does get copied into RNA — the molecule that carries DNA’s messages to the rest of the cell.

Scientists have been trying to figure out just what this RNA might be doing, if anything. In 2008, MIT researchers led by Institute Professor Phillip Sharp discovered that much of this RNA is generated through a process called divergent expression, through which cells read their DNA in both directions moving away from a given starting point.

In a new paper appearing in Nature on June 23, Sharp and colleagues describe how cells initiate but then halt the copying of RNA in the upstream, or non-protein-coding direction, while allowing it to continue in the direction in which genes are correctly read. The finding helps to explain the existence of many recently discovered types of short strands of RNA whose function is unknown.

“This is part of an RNA revolution where we’re seeing different RNAs and new RNAs that we hadn’t suspected were present in cells, and trying to understand what role they have in the health of the cell or the viability of the cell,” says Sharp, who is a member of MIT’s Koch Institute for Integrative Cancer Research. “It gives us a whole new appreciation of the balance of the fundamental processes that allow cells to function.”

Graduate students Albert Almada and Xuebing Wu are the lead authors of the paper. Christopher Burge, a professor of biology and biological engineering, and undergraduate Andrea Kriz are also authors.

Choosing direction

DNA, which is housed within the nucleus of cells, controls cellular activity by coding for the production of RNAs and proteins. To exert this control, the genetic information encoded by DNA must first be copied, or transcribed, into messenger RNA (mRNA).

When the DNA double helix unwinds to reveal its genetic messages, RNA transcription can proceed in either direction. To initiate this copying, an enzyme called RNA polymerase latches on to the DNA at a spot known as the promoter. The RNA polymerase then moves along the strand, building the mRNA chain as it goes.

When the RNA polymerase reaches a stop signal at the end of a gene, it halts transcription and adds to the mRNA a sequence of bases known as a poly-A tail, which consists of a long string of the genetic base adenine. This process, known as polyadenylation, helps to prepare the mRNA molecule to be exported from the cell’s nucleus.

By sequencing the mRNA transcripts of mouse embryonic stem cells, the researchers discovered that polyadenylation also plays a major role in halting the transcription of upstream, noncoding DNA sequences. They found that these regions have a high density of signal sequences for polyadenylation, which prompts enzymes to chop up the RNA before it gets very long. Stretches of DNA that code for genes have a low density of these signal sequences.

The researchers also found another factor that influences whether transcription is allowed to continue. It has been recently shown that when a cellular factor known as U1 snRNP binds to RNA, polyadenylation is suppressed. The new MIT study found that genes have a higher concentration of binding sites for U1 snRNP than noncoding sequences, allowing gene transcription to continue uninterrupted.

The work demonstrates the important role of U1 snRNP in protecting mRNA as it is transcribed from genes and in preventing the cell from unnecessary copying of non-protein-coding DNA, says Gideon Dreyfuss, a professor of biochemistry and biophysics at the University of Pennsylvania School of Medicine.

“They’ve identified a very likely mechanism for early termination of these upstream RNAs by depriving them of U1 snRNP suppression of polyadenylation and cleavage,” says Dreyfuss, who was not part of the research team.

A widespread phenomenon

The function of all of this upstream noncoding RNA is still a subject of much investigation. “That transcriptional process could produce an RNA that has some function, or it could be a product of the nature of the biochemical reaction. This will be debated for a long time,” Sharp says.

His lab is now exploring the relationship between this transcription process and the observation of large numbers of so-called long noncoding RNAs (lncRNAs). He plans to investigate the mechanisms that control the synthesis of such RNAs and try to determine their functions.

“Once you see some data like this, it raises many more questions to be investigated, which I’m hoping will lead us to deeper insights into how our cells carry out their normal functions and how they change in malignancy,” Sharp says.

The research was funded by the National Institutes of Health, the National Cancer Institute and the National Institute of General Medical Sciences.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Wednesday, April 27, 2016
Why Some Tumors Withstand Treatment
Mechanism uncovered that allows cancer cells to evade targeted therapies.
Thursday, March 17, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
Wednesday, February 03, 2016
Faster Drug Discovery?
Startup develops more cost-effective test for assessing how cells respond to chemicals.
Friday, January 29, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
Tracing a Cellular Family Tree
New technique allows tracking of gene expression over generations of cells as they specialize.
Wednesday, January 06, 2016
New Device Uses Carbon Nanotubes to Snag Molecules
Nanotube “forest” in a microfluidic channel may help detect rare proteins and viruses.
Tuesday, December 22, 2015
Scaling Up Synthetic-Biology Innovation
MIT professor’s startup makes synthesizing genes many times more cost effective.
Monday, December 14, 2015
“Kill Switches” Shut Down Engineered Bacteria
Synthetic biology technique could make it safer to put engineered microbes to work outside of the lab.
Monday, December 14, 2015
Drug-Resistance Mechanism in Tumor Cells Unravelled
Targeting the RNA-binding protein that promotes resistance could lead to better cancer therapies.
Friday, October 23, 2015
Learning About Human Health Using Sewage
PhD student Mariana Matus studies human waste to understand individual and community health.
Thursday, September 17, 2015
Real-Time Data for Cancer Therapy
Biochemical sensor implanted at initial biopsy could allow doctors to better monitor and adjust cancer treatments.
Thursday, August 06, 2015
Bacterial Computing
The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
Monday, July 13, 2015
Researchers Develop Genetic Tools to Engineer Common Gut Bacterium
Researchers from the Massachusetts Institute of Technology have developed genetic parts that can be combined to program the commensal gut bacterium Bacteroides thetaiotaomicron.
Friday, July 10, 2015
Scientific News
Faster, Cheaper Way to Produce New Antibiotics
A novel way of synthesising a promising new antibiotic has been identified by scientists at the University of Bristol.
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
Autism, Cancer Share a Remarkable Number of Risk Genes
Researchers with the UC Davis Comprehensive Cancer Center, MIND Institute identify more than 40 common genes.
Number Of Known Genetic Risk Factors For Endometrial Cancer Doubled
An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.
FNIH Launches Project to Evaluate Biomarkers in Cancer Patients
Company has announced that it has launched a new project to evaluate the effectiveness of liquid biopsies as biomarkers in colorectal cancer patients.
Genetic Risk Factors of Disparate Diseases Share Similar Biological Underpinnings
Penn Institute for Biomedical Informatics and colleagues identify "roadmap" of disease mechanisms to identify candidate drug targets.
Childhood Asthma Research Receives $2M
Research into the impact of a child’s upbringing and social and physical environments on the development of asthma will receive $2 million to tackle the condition that affects as many as one in three Canadians.
Making Precision Medicine a Reality
Researchers are one step closer to understanding the genetic and biological basis of diseases like cancer, diabetes, Alzheimer’s and rheumatoid arthritis – and identifying new drug targets and therapies.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
Potential “Good Fat” Biomarker
New method to measure the activity of energy consuming brown fat cells could ease the testing weight loss drugs.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!